Egg and milk exposure during pregnancy and food reactions in grandchildren
Authors: Ida Mogensen, Charlotta Flodström, Anna Nopp, Erik Melén, Anna Bergström, Inger Kull
Journal: Allergy (2022)

To the Editor, The origins of food allergy and food-related symptoms are to a large extent not understood, despite their large impact on public health.1 Our aim was to evaluate whether avoidance of intake of egg and milk during the last trimester of pregnancy compared to a high intake, associate to food reactions and IgE sensitization against egg and milk in the exposed woman's grandchildren. The KUG (Kost under graviditet, ‘Diet During Pregnancy’) study was initially an open-label randomized trial with the intervention conducted between 1983 and 1985,2 with the aim to study whether egg and milk exclusion prevent allergic disease in the offspring. The included study population were pregnant women with a history of bronchial asthma and/or rhino-conjunctivitis when exposed to animal dander and/or tree or grass pollen. They were randomized to a diet avoiding egg and milk (avoiding group) or a diet containing 1 egg and 0.5 L of milk per day (exposed group) during the last trimester of pregnancy.3, 4 Over 30 years later, 78 grandchildren were examined by a study physician, reactions to egg or milk ever were parental-reported and IgE against egg and milk measured (detailed method in Appendix S1). The avoiding group (n = 27) had 52 grandchildren and the exposed group (n = 19) 26 grandchildren, Figure 1. There were no significant differences in baseline characteristics between the grandchildren from the two exposure groups Table 1. We found a higher prevalence of reported reactions to egg among the grandchildren in the avoiding group n = 8/52 (15%) compared to the exposed group 0/26 (0%), p = .047. There was also a higher prevalence of reported reactions to egg and/or milk in the avoiding group n = 16/52 (31%) than in the exposed group n = 1/26 (3.9%) (p = .008). All participants who reported reactions to egg or milk with simultaneously elevated IgE belonged to the avoiding group, Table 1. The prevalence of atopic dermatitis was 24% in the avoiding group compared to 8% in the exposed group, although not a significant difference, however, could this suggest a higher risk in this group for food reactions. In stratified analyses, the association between avoidance of egg and milk and higher prevalence of reactions to milk or egg and/or milk was present for maternal grandmothers' grandchildren but not for paternal grandmothers' (Figure S1A,B). In the second generation, no participant in the exposed group reported reactions against egg or milk at 5 years of age (although no significant differences between the groups; Table S1). Five women from the first generation with included grandchildren did not follow the analysis per protocol, two in the avoiding group and three in the exposed group, however, not affecting the associations (Table S2). Including only the oldest child from each family did not affect the associations either (Table S3). Not all children with ever-reported reactions had IgE against egg or milk. Reasons for this could be the wide age range, where some children might have grown out of their allergy,5 and IgE only being tested in a subgroup. Others might react due to other mechanisms. The association was only present for the maternal grandmother's grandchildren, possibly suggesting epigenetic mechanisms attributed to changes in the foetal oocytes to be at play, previously seen in studies on smoking.6 In conclusion, we found the lowest prevalence of egg and milk reactions in children whose grandmother did eat a diet rich in egg and milk during the third trimester of pregnancy. Despite a limited number of participants, our results suggest diets excluding food items, especially containing allergens, to be potentially associated with food reactions in later generations. We would like to thank the late associate professor Gunnar Lilja for initiating and maintaining this cohort. We further thank all the children, parents and grandparents for contributing to this research. The Swedish Asthma and Allergy Association, F2018-0026. Ellen, Walter och Lennart Hesselmans stiftelse. EM has received personal fees from ALK, AstraZeneca, Novartis and Sanofi outside the submitted work. None of the other authors have any conflicts of interests to report. Appendix S1 Tables S1–S3 Figure S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.